rs149868979
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBP4
The NM_000336.3(SCNN1B):c.1688G>A(p.Arg563Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R563W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000336.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1B | NM_000336.3 | c.1688G>A | p.Arg563Gln | missense_variant | 13/13 | ENST00000343070.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1B | ENST00000343070.7 | c.1688G>A | p.Arg563Gln | missense_variant | 13/13 | 1 | NM_000336.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152250Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000147 AC: 37AN: 251322Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135866
GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461840Hom.: 1 Cov.: 32 AF XY: 0.0000825 AC XY: 60AN XY: 727230
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152368Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74514
ClinVar
Submissions by phenotype
Low renin, low aldosterone hypertension Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneID Lab - Advanced Molecular Diagnostics | Mar 10, 2018 | This variant results in an amino acid alteration, replacing an arginine(R) with a glutamine (Q) at position 563, written as p.Arg563Gln or p.Q889H. . in silico prediction algorithms does not provide uniform data regarding the effect of this change on protein structure and function, and it has not been reported in the Clin Var Database (NCBI National Library of Medicine, NIH) but it has been described in 16 alleles out of 121124, in the ExAC database, the majority (9) belonging to heterozygous carries of Latino origin. The variant has been associated with low-renin, low-aldosterone hypertension in South African black and mixed-ancestry individuals, the authors conclude that only a portion of subjects with the R563Q allele fully express the Liddle’s syndrome phenotype (J Hypertens. 2003 May;21(5):921-6). Moreover, there is a positive correlation with pre-eclampsia in this population (BJOG. 2006 May;113(5):595-8). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at